A 19 month old male presented with gradually progressive erythematous, atrophic plaques studded with firm papules from 3 months of age. These began at the right parietal scalp and have progressed to involve the thigh, trunk and buttocks. They are asymptomatic and there was no preceding rash nor trauma. There is no family history of skin conditions. His past medical history includes intrauterine growth restriction and he remains on the 0.4th centile for weight, length and head circumference.
Histopathology revealed two foci of calcification with ossification in the dermis. Blood tests revealed a mild normocytic anaemia and low insulin like growth factor 1 of uncertain significance. No cause for metastatic calcification was identified. Connective tissue screen was normal and inflammatory markers not raised. A hip, pelvis and femur X-ray were normal. Serum genetic studies were performed for a GNAS gene mutation. Preliminary results have revealed a heterozygous deletion of exons 2-13 in GNAS.
This clinical picture and preliminary genetics testing is consistent with Progressive Osseous Heteroplasia, an ultra-rare genetic condition commonly associated with an inactivating GNAS mutation on the paternal chromosome. Progressive Osseous Heteroplasia is part of a spectrum of related genetic disorders, which includes Albright's Hereditary Osteodystrophy and Plate-like Osteoma Cutis that share common features of superficial extra-skeletal ossification associated with inactivating mutations of GNAS1. The GNAS gene regulates adenyl cyclase activity, which is believed to be a negative regulator of bone formation2. Paternal GNAS mutations have also been shown to lead to intra-uterine growth restriction3.